AU2022296794A1 - Interleukin-15 based immunocytokines - Google Patents
Interleukin-15 based immunocytokines Download PDFInfo
- Publication number
- AU2022296794A1 AU2022296794A1 AU2022296794A AU2022296794A AU2022296794A1 AU 2022296794 A1 AU2022296794 A1 AU 2022296794A1 AU 2022296794 A AU2022296794 A AU 2022296794A AU 2022296794 A AU2022296794 A AU 2022296794A AU 2022296794 A1 AU2022296794 A1 AU 2022296794A1
- Authority
- AU
- Australia
- Prior art keywords
- antibody
- seq
- immunocytokine
- cells
- rli
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229940127130 immunocytokine Drugs 0.000 title claims abstract description 297
- 102000003812 Interleukin-15 Human genes 0.000 title claims abstract description 100
- 108090000172 Interleukin-15 Proteins 0.000 title claims abstract description 100
- 230000035772 mutation Effects 0.000 claims description 215
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 claims description 119
- 206010028980 Neoplasm Diseases 0.000 claims description 103
- 102220578645 Chorion-specific transcription factor GCMb_N65A_mutation Human genes 0.000 claims description 68
- 108010002350 Interleukin-2 Proteins 0.000 claims description 61
- 102000000588 Interleukin-2 Human genes 0.000 claims description 61
- 102100040678 Programmed cell death protein 1 Human genes 0.000 claims description 53
- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims description 51
- 101001133056 Homo sapiens Mucin-1 Proteins 0.000 claims description 50
- 102100034256 Mucin-1 Human genes 0.000 claims description 50
- 239000012636 effector Substances 0.000 claims description 48
- 230000002829 reductive effect Effects 0.000 claims description 47
- 238000001727 in vivo Methods 0.000 claims description 42
- 238000006467 substitution reaction Methods 0.000 claims description 40
- 230000013595 glycosylation Effects 0.000 claims description 37
- 238000006206 glycosylation reaction Methods 0.000 claims description 37
- 239000000556 agonist Substances 0.000 claims description 36
- 230000001965 increasing effect Effects 0.000 claims description 36
- 102000004127 Cytokines Human genes 0.000 claims description 35
- 108090000695 Cytokines Proteins 0.000 claims description 35
- 102000005962 receptors Human genes 0.000 claims description 33
- 108020003175 receptors Proteins 0.000 claims description 33
- 108010053727 Interleukin-15 Receptor alpha Subunit Proteins 0.000 claims description 30
- 150000001413 amino acids Chemical class 0.000 claims description 30
- 235000001014 amino acid Nutrition 0.000 claims description 28
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 26
- 239000005557 antagonist Substances 0.000 claims description 25
- 230000014509 gene expression Effects 0.000 claims description 25
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 22
- 239000000427 antigen Substances 0.000 claims description 19
- 230000006240 deamidation Effects 0.000 claims description 18
- 108091007433 antigens Proteins 0.000 claims description 17
- 102000036639 antigens Human genes 0.000 claims description 17
- 150000002333 glycines Chemical class 0.000 claims description 14
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 13
- 229920001184 polypeptide Polymers 0.000 claims description 13
- 102000016359 Fibronectins Human genes 0.000 claims description 11
- 108010067306 Fibronectins Proteins 0.000 claims description 11
- -1 LGLR2 Proteins 0.000 claims description 11
- 108020001507 fusion proteins Proteins 0.000 claims description 11
- 102000037865 fusion proteins Human genes 0.000 claims description 11
- 229940045513 CTLA4 antagonist Drugs 0.000 claims description 9
- 102220604023 Homeobox protein SIX3_N79Q_mutation Human genes 0.000 claims description 9
- 230000007541 cellular toxicity Effects 0.000 claims description 9
- 230000001419 dependent effect Effects 0.000 claims description 9
- 230000002519 immonomodulatory effect Effects 0.000 claims description 9
- 102200104661 rs73598374 Human genes 0.000 claims description 9
- 102220578647 Chorion-specific transcription factor GCMb_N65D_mutation Human genes 0.000 claims description 8
- 235000004400 serine Nutrition 0.000 claims description 8
- 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 claims description 7
- 102100033728 Tumor necrosis factor receptor superfamily member 18 Human genes 0.000 claims description 7
- 102200042996 rs1057521927 Human genes 0.000 claims description 7
- 102220053806 rs121918461 Human genes 0.000 claims description 7
- 150000003355 serines Chemical class 0.000 claims description 7
- 102220479509 Proteasome inhibitor PI31 subunit_D8A_mutation Human genes 0.000 claims description 6
- 210000004899 c-terminal region Anatomy 0.000 claims description 6
- 238000004113 cell culture Methods 0.000 claims description 6
- 102200155472 rs397507510 Human genes 0.000 claims description 6
- 102220114664 rs886038997 Human genes 0.000 claims description 6
- 102000017578 LAG3 Human genes 0.000 claims description 5
- 230000004481 post-translational protein modification Effects 0.000 claims description 5
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 claims description 4
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 4
- 108700012439 CA9 Proteins 0.000 claims description 4
- 102100024423 Carbonic anhydrase 9 Human genes 0.000 claims description 4
- 101100385253 Chiloscyllium indicum GM1 gene Proteins 0.000 claims description 4
- 102000012804 EPCAM Human genes 0.000 claims description 4
- 101150084967 EPCAM gene Proteins 0.000 claims description 4
- 102220531889 Glucose-fructose oxidoreductase domain-containing protein 1_K10A_mutation Human genes 0.000 claims description 4
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 claims description 4
- 102100032530 Glypican-3 Human genes 0.000 claims description 4
- 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 claims description 4
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 4
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 claims description 4
- 101001014668 Homo sapiens Glypican-3 Proteins 0.000 claims description 4
- 101001103039 Homo sapiens Inactive tyrosine-protein kinase transmembrane receptor ROR1 Proteins 0.000 claims description 4
- 101001103036 Homo sapiens Nuclear receptor ROR-alpha Proteins 0.000 claims description 4
- 206010029113 Neovascularisation Diseases 0.000 claims description 4
- 101150057140 TACSTD1 gene Proteins 0.000 claims description 4
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 4
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 claims description 4
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 claims description 3
- 102220578068 ATPase MORC2_G78L_mutation Human genes 0.000 claims description 3
- 102100035990 Adenosine receptor A2a Human genes 0.000 claims description 3
- 101150013553 CD40 gene Proteins 0.000 claims description 3
- 102220594337 Cytochrome P450 4F2_S7Y_mutation Human genes 0.000 claims description 3
- 102220513642 Diphosphoinositol polyphosphate phosphohydrolase 1_G78V_mutation Human genes 0.000 claims description 3
- 102100037241 Endoglin Human genes 0.000 claims description 3
- 108010036395 Endoglin Proteins 0.000 claims description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 3
- 102100035139 Folate receptor alpha Human genes 0.000 claims description 3
- 102220532061 Glucose-fructose oxidoreductase domain-containing protein 1_K11A_mutation Human genes 0.000 claims description 3
- 108010007707 Hepatitis A Virus Cellular Receptor 2 Proteins 0.000 claims description 3
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 claims description 3
- 101000783751 Homo sapiens Adenosine receptor A2a Proteins 0.000 claims description 3
- 101001023230 Homo sapiens Folate receptor alpha Proteins 0.000 claims description 3
- 101001039113 Homo sapiens Leucine-rich repeat-containing protein 15 Proteins 0.000 claims description 3
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 claims description 3
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 3
- 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 claims description 3
- 102000002698 KIR Receptors Human genes 0.000 claims description 3
- 108010043610 KIR Receptors Proteins 0.000 claims description 3
- 102100040645 Leucine-rich repeat-containing protein 15 Human genes 0.000 claims description 3
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 3
- 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 claims description 3
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims description 3
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 3
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 3
- 108091008034 costimulatory receptors Proteins 0.000 claims description 3
- 210000002744 extracellular matrix Anatomy 0.000 claims description 3
- 230000001506 immunosuppresive effect Effects 0.000 claims description 3
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims description 3
- 102220319049 rs1032793565 Human genes 0.000 claims description 3
- 102200077457 rs36088178 Human genes 0.000 claims description 3
- 102200038092 rs6759892 Human genes 0.000 claims description 3
- 102220128075 rs144664869 Human genes 0.000 claims 2
- 102000007346 Hepatitis A Virus Cellular Receptor 2 Human genes 0.000 claims 1
- 102100039614 Nuclear receptor ROR-alpha Human genes 0.000 claims 1
- 102000039446 nucleic acids Human genes 0.000 abstract description 15
- 108020004707 nucleic acids Proteins 0.000 abstract description 15
- 150000007523 nucleic acids Chemical class 0.000 abstract description 15
- 239000013598 vector Substances 0.000 abstract description 13
- 238000000034 method Methods 0.000 abstract description 10
- 230000002483 superagonistic effect Effects 0.000 abstract description 9
- 210000004027 cell Anatomy 0.000 description 185
- 101100433751 Arabidopsis thaliana ABCE2 gene Proteins 0.000 description 117
- 230000000694 effects Effects 0.000 description 116
- 210000001744 T-lymphocyte Anatomy 0.000 description 90
- 241000699670 Mus sp. Species 0.000 description 51
- 210000000822 natural killer cell Anatomy 0.000 description 51
- 229960002621 pembrolizumab Drugs 0.000 description 50
- 238000011282 treatment Methods 0.000 description 40
- 241000699666 Mus <mouse, genus> Species 0.000 description 39
- 238000000684 flow cytometry Methods 0.000 description 36
- 230000035755 proliferation Effects 0.000 description 36
- 108090000623 proteins and genes Proteins 0.000 description 34
- 230000006870 function Effects 0.000 description 31
- 230000004913 activation Effects 0.000 description 29
- 229960004641 rituximab Drugs 0.000 description 29
- 238000003556 assay Methods 0.000 description 27
- 210000002865 immune cell Anatomy 0.000 description 26
- 102000004169 proteins and genes Human genes 0.000 description 25
- 235000018102 proteins Nutrition 0.000 description 24
- 238000011740 C57BL/6 mouse Methods 0.000 description 23
- 241000282567 Macaca fascicularis Species 0.000 description 22
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 22
- 210000000952 spleen Anatomy 0.000 description 22
- 239000003814 drug Substances 0.000 description 21
- 238000000338 in vitro Methods 0.000 description 21
- 210000002966 serum Anatomy 0.000 description 21
- 229940079593 drug Drugs 0.000 description 20
- 229940024606 amino acid Drugs 0.000 description 19
- 210000004369 blood Anatomy 0.000 description 19
- 239000008280 blood Substances 0.000 description 19
- 241001465754 Metazoa Species 0.000 description 18
- 241001529936 Murinae Species 0.000 description 17
- 101000611935 Mus musculus Programmed cell death protein 1 Proteins 0.000 description 16
- 238000004458 analytical method Methods 0.000 description 16
- 230000004663 cell proliferation Effects 0.000 description 15
- 230000000259 anti-tumor effect Effects 0.000 description 14
- 239000002609 medium Substances 0.000 description 14
- 239000006228 supernatant Substances 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 108010074708 B7-H1 Antigen Proteins 0.000 description 13
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 13
- 230000005847 immunogenicity Effects 0.000 description 13
- 238000004519 manufacturing process Methods 0.000 description 13
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 12
- 230000006052 T cell proliferation Effects 0.000 description 12
- 102220419271 c.78G>A Human genes 0.000 description 12
- 230000002708 enhancing effect Effects 0.000 description 12
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 12
- 238000002347 injection Methods 0.000 description 12
- 239000007924 injection Substances 0.000 description 12
- 238000007912 intraperitoneal administration Methods 0.000 description 12
- 210000001165 lymph node Anatomy 0.000 description 12
- 238000012986 modification Methods 0.000 description 12
- 230000004044 response Effects 0.000 description 12
- 230000000638 stimulation Effects 0.000 description 12
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 12
- 210000004881 tumor cell Anatomy 0.000 description 12
- 239000000499 gel Substances 0.000 description 11
- 238000011534 incubation Methods 0.000 description 11
- 230000004048 modification Effects 0.000 description 11
- 238000002965 ELISA Methods 0.000 description 10
- 241000282412 Homo Species 0.000 description 10
- 238000011156 evaluation Methods 0.000 description 10
- 238000007920 subcutaneous administration Methods 0.000 description 10
- 230000008685 targeting Effects 0.000 description 10
- 238000004166 bioassay Methods 0.000 description 9
- 230000004927 fusion Effects 0.000 description 9
- 230000006698 induction Effects 0.000 description 9
- 238000010172 mouse model Methods 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 230000003042 antagnostic effect Effects 0.000 description 8
- 230000000903 blocking effect Effects 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 230000003247 decreasing effect Effects 0.000 description 8
- 210000004698 lymphocyte Anatomy 0.000 description 8
- 238000000926 separation method Methods 0.000 description 8
- 241000894007 species Species 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 238000001262 western blot Methods 0.000 description 8
- 201000011510 cancer Diseases 0.000 description 7
- 230000000875 corresponding effect Effects 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 230000002195 synergetic effect Effects 0.000 description 7
- 238000012546 transfer Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 6
- 239000004472 Lysine Substances 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 6
- 230000003013 cytotoxicity Effects 0.000 description 6
- 231100000135 cytotoxicity Toxicity 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 230000003285 pharmacodynamic effect Effects 0.000 description 6
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
- 238000010186 staining Methods 0.000 description 6
- 230000004936 stimulating effect Effects 0.000 description 6
- 229950007157 zolbetuximab Drugs 0.000 description 6
- 208000035473 Communicable disease Diseases 0.000 description 5
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 5
- 101001055157 Homo sapiens Interleukin-15 Proteins 0.000 description 5
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 5
- 230000004988 N-glycosylation Effects 0.000 description 5
- 230000001270 agonistic effect Effects 0.000 description 5
- 238000005251 capillar electrophoresis Methods 0.000 description 5
- 238000000423 cell based assay Methods 0.000 description 5
- 229960005395 cetuximab Drugs 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000012997 ficoll-paque Substances 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 238000005734 heterodimerization reaction Methods 0.000 description 5
- 102000056003 human IL15 Human genes 0.000 description 5
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 230000002035 prolonged effect Effects 0.000 description 5
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 4
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 4
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 4
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 4
- 108010087819 Fc receptors Proteins 0.000 description 4
- 102000009109 Fc receptors Human genes 0.000 description 4
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 4
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 4
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 4
- 108060003951 Immunoglobulin Proteins 0.000 description 4
- 108010002586 Interleukin-7 Proteins 0.000 description 4
- 230000006044 T cell activation Effects 0.000 description 4
- 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 230000002001 anti-metastasis Effects 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 4
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
- 102000018358 immunoglobulin Human genes 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 230000001613 neoplastic effect Effects 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 238000013207 serial dilution Methods 0.000 description 4
- 230000011664 signaling Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 3
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 3
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 108700004922 F42A Proteins 0.000 description 3
- 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 3
- 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 description 3
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 3
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 3
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 3
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 description 3
- 102100039615 Inactive tyrosine-protein kinase transmembrane receptor ROR1 Human genes 0.000 description 3
- 108090000978 Interleukin-4 Proteins 0.000 description 3
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 3
- 102220505697 Palmitoyl-protein thioesterase 1_Y45F_mutation Human genes 0.000 description 3
- 102220495631 Putative uncharacterized protein LOC645739_F42A_mutation Human genes 0.000 description 3
- 239000013614 RNA sample Substances 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 102220610852 Thialysine N-epsilon-acetyltransferase_L72G_mutation Human genes 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102100040247 Tumor necrosis factor Human genes 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 238000002784 cytotoxicity assay Methods 0.000 description 3
- 231100000263 cytotoxicity test Toxicity 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 210000004475 gamma-delta t lymphocyte Anatomy 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 239000012642 immune effector Substances 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 229940121354 immunomodulator Drugs 0.000 description 3
- 230000003116 impacting effect Effects 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 230000000415 inactivating effect Effects 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 210000003071 memory t lymphocyte Anatomy 0.000 description 3
- 230000001394 metastastic effect Effects 0.000 description 3
- 206010061289 metastatic neoplasm Diseases 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 229960003301 nivolumab Drugs 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 229950010131 puromycin Drugs 0.000 description 3
- 238000009097 single-agent therapy Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Natural products CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 3
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 3
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 3
- 108010057840 ALT-803 Proteins 0.000 description 2
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 2
- 102000002029 Claudin Human genes 0.000 description 2
- 108050009302 Claudin Proteins 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 101150027068 DEGS1 gene Proteins 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 102000006471 Fucosyltransferases Human genes 0.000 description 2
- 108010019236 Fucosyltransferases Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 101710083479 Hepatitis A virus cellular receptor 2 homolog Proteins 0.000 description 2
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 2
- 101001003140 Homo sapiens Interleukin-15 receptor subunit alpha Proteins 0.000 description 2
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 2
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 2
- 101000628562 Homo sapiens Serine/threonine-protein kinase STK11 Proteins 0.000 description 2
- 101150089646 Hpdl gene Proteins 0.000 description 2
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 2
- 108010000837 Janus Kinase 1 Proteins 0.000 description 2
- 101150030213 Lag3 gene Proteins 0.000 description 2
- 102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 description 2
- 229940125568 MGD013 Drugs 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 238000003559 RNA-seq method Methods 0.000 description 2
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 2
- 102100026715 Serine/threonine-protein kinase STK11 Human genes 0.000 description 2
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 2
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 2
- 102100033438 Tyrosine-protein kinase JAK1 Human genes 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 description 2
- 239000012911 assay medium Substances 0.000 description 2
- 229960003852 atezolizumab Drugs 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 229950002916 avelumab Drugs 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
- 238000004737 colorimetric analysis Methods 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000001351 cycling effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 2
- 238000010201 enrichment analysis Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 229940115924 etigilimab Drugs 0.000 description 2
- 238000010195 expression analysis Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 102000046699 human CD14 Human genes 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 235000003642 hunger Nutrition 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 229960005386 ipilimumab Drugs 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 239000012160 loading buffer Substances 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 239000002096 quantum dot Substances 0.000 description 2
- 229940121484 relatlimab Drugs 0.000 description 2
- 102220104466 rs879254287 Human genes 0.000 description 2
- 239000012146 running buffer Substances 0.000 description 2
- 239000012723 sample buffer Substances 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 230000037351 starvation Effects 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229950007133 tiragolumab Drugs 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000010474 transient expression Effects 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
- 229940125559 AB154 Drugs 0.000 description 1
- 229940125554 ASP-8374 Drugs 0.000 description 1
- 102100036664 Adenosine deaminase Human genes 0.000 description 1
- 239000012117 Alexa Fluor 700 Substances 0.000 description 1
- 102100021266 Alpha-(1,6)-fucosyltransferase Human genes 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 238000011725 BALB/c mouse Methods 0.000 description 1
- 229940125556 BGB-A1217 Drugs 0.000 description 1
- 229940125565 BMS-986016 Drugs 0.000 description 1
- 229940125557 BMS-986207 Drugs 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 201000005488 Capillary Leak Syndrome Diseases 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- RTXOFQZKPXMALH-PRHODGIISA-N Cefzon Chemical compound S1C(N)=NC(C(=NO)C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 RTXOFQZKPXMALH-PRHODGIISA-N 0.000 description 1
- 102000000989 Complement System Proteins Human genes 0.000 description 1
- 108010069112 Complement System Proteins Proteins 0.000 description 1
- 238000000018 DNA microarray Methods 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- LQEBEXMHBLQMDB-UHFFFAOYSA-N GDP-L-fucose Natural products OC1C(O)C(O)C(C)OC1OP(O)(=O)OP(O)(=O)OCC1C(O)C(O)C(N2C3=C(C(N=C(N)N3)=O)N=C2)O1 LQEBEXMHBLQMDB-UHFFFAOYSA-N 0.000 description 1
- LQEBEXMHBLQMDB-JGQUBWHWSA-N GDP-beta-L-fucose Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](C)O[C@@H]1OP(O)(=O)OP(O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=C(C(NC(N)=N3)=O)N=C2)O1 LQEBEXMHBLQMDB-JGQUBWHWSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 101000819490 Homo sapiens Alpha-(1,6)-fucosyltransferase Proteins 0.000 description 1
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
- 101000913761 Homo sapiens Serine/threonine-protein kinase ICK Proteins 0.000 description 1
- 229940125561 IBI-939 Drugs 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 1
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 102100020773 Immunoglobulin kappa variable 1-12 Human genes 0.000 description 1
- 108010066719 Interleukin Receptor Common gamma Subunit Proteins 0.000 description 1
- 102000018682 Interleukin Receptor Common gamma Subunit Human genes 0.000 description 1
- 108010002335 Interleukin-9 Proteins 0.000 description 1
- 102000042838 JAK family Human genes 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 1
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 1
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 239000012515 MabSelect SuRe Substances 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- 238000011786 NMRI nude mouse Methods 0.000 description 1
- 230000004989 O-glycosylation Effects 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- 241000235648 Pichia Species 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 229940125566 REGN3767 Drugs 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 102000001712 STAT5 Transcription Factor Human genes 0.000 description 1
- 108010029477 STAT5 Transcription Factor Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102100026621 Serine/threonine-protein kinase ICK Human genes 0.000 description 1
- 241000872198 Serjania polyphylla Species 0.000 description 1
- 239000012505 Superdex™ Substances 0.000 description 1
- 229940125564 Sym022 Drugs 0.000 description 1
- 208000031932 Systemic capillary leak syndrome Diseases 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 108700012920 TNF Proteins 0.000 description 1
- 229940125567 TSR-033 Drugs 0.000 description 1
- 102000008579 Transposases Human genes 0.000 description 1
- 108010020764 Transposases Proteins 0.000 description 1
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000006786 activation induced cell death Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000004721 adaptive immunity Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000002494 anti-cea effect Effects 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 238000011091 antibody purification Methods 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229950005725 arcitumomab Drugs 0.000 description 1
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 238000011953 bioanalysis Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000001818 capillary gel electrophoresis Methods 0.000 description 1
- 239000013019 capto adhere Substances 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000034196 cell chemotaxis Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000017455 cell-cell adhesion Effects 0.000 description 1
- 230000005889 cellular cytotoxicity Effects 0.000 description 1
- 230000008614 cellular interaction Effects 0.000 description 1
- 229940121420 cemiplimab Drugs 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 230000005574 cross-species transmission Effects 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 229960002204 daratumumab Drugs 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000009615 deamination Effects 0.000 description 1
- 238000006481 deamination reaction Methods 0.000 description 1
- 230000022811 deglycosylation Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 230000009274 differential gene expression Effects 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 238000005315 distribution function Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 229950009791 durvalumab Drugs 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000013020 final formulation Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000033581 fucosylation Effects 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 101150023212 fut8 gene Proteins 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 150000004676 glycans Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 102000053350 human FCGR3B Human genes 0.000 description 1
- 102000048362 human PDCD1 Human genes 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 229940121569 ieramilimab Drugs 0.000 description 1
- 230000005931 immune cell recruitment Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 108040002039 interleukin-15 receptor activity proteins Proteins 0.000 description 1
- 102000008616 interleukin-15 receptor activity proteins Human genes 0.000 description 1
- 108010074108 interleukin-21 Proteins 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229950007752 isatuximab Drugs 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 229950003135 margetuximab Drugs 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229950008001 matuzumab Drugs 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 238000001728 nano-filtration Methods 0.000 description 1
- 210000000581 natural killer T-cell Anatomy 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
- 229950010203 nimotuzumab Drugs 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 229960003347 obinutuzumab Drugs 0.000 description 1
- 229950005751 ocrelizumab Drugs 0.000 description 1
- 229960002450 ofatumumab Drugs 0.000 description 1
- 238000007427 paired t-test Methods 0.000 description 1
- 229960001972 panitumumab Drugs 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 229950010773 pidilizumab Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 229960003876 ranibizumab Drugs 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 229940121325 samrotamab Drugs 0.000 description 1
- 229940060040 selicrelumab Drugs 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000009450 sialylation Effects 0.000 description 1
- 229950008684 sibrotuzumab Drugs 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 229940121497 sintilimab Drugs 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229950007213 spartalizumab Drugs 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000012536 storage buffer Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940126625 tavolimab Drugs 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229950007123 tislelizumab Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229940121514 toripalimab Drugs 0.000 description 1
- 229960005267 tositumomab Drugs 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 229950007217 tremelimumab Drugs 0.000 description 1
- 238000009966 trimming Methods 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 229950004593 ublituximab Drugs 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229950005972 urelumab Drugs 0.000 description 1
- 229950003520 utomilumab Drugs 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 229940020434 vibostolimab Drugs 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 229950008250 zalutumumab Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/5443—IL-15
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
- C07K14/7155—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons for interleukins [IL]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/32—Fusion polypeptide fusions with soluble part of a cell surface receptor, "decoy receptors"
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Cell Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Toxicology (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Virology (AREA)
- Biotechnology (AREA)
- Developmental Biology & Embryology (AREA)
- Biomedical Technology (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP21181271 | 2021-06-23 | ||
| EP21181271.4 | 2021-06-23 | ||
| EP22163748.1 | 2022-03-23 | ||
| EP22163748 | 2022-03-23 | ||
| PCT/EP2022/067236 WO2022268983A2 (fr) | 2021-06-23 | 2022-06-23 | Immunocytokines à base d'interleukine-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2022296794A1 true AU2022296794A1 (en) | 2023-12-14 |
Family
ID=82361370
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2022296794A Pending AU2022296794A1 (en) | 2021-06-23 | 2022-06-23 | Interleukin-15 based immunocytokines |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP4359428A2 (fr) |
| KR (1) | KR20240024242A (fr) |
| AU (1) | AU2022296794A1 (fr) |
| BR (1) | BR112023027312A2 (fr) |
| CA (1) | CA3221886A1 (fr) |
| IL (1) | IL309533A (fr) |
| WO (1) | WO2022268983A2 (fr) |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI259837B (en) | 1998-05-11 | 2006-08-11 | Eidgenossische Tech Hochscule | Specific binding molecules for scintigraphy, conjugates containing them and therapeutic method for treatment of angiogenesis |
| US20100082438A1 (en) | 2008-10-01 | 2010-04-01 | Ronnie Jack Garmon | Methods and systems for customer performance scoring |
| US20110318302A1 (en) | 2009-01-07 | 2011-12-29 | Kathrin Schwager | Cancer Treatment |
| AU2014232501C1 (en) * | 2013-03-15 | 2021-04-22 | Xencor, Inc. | Heterodimeric proteins |
| EP2988784A1 (fr) | 2013-04-25 | 2016-03-02 | Philogen S.p.A. | Conjugués anticorps-médicament |
| WO2017095805A1 (fr) | 2015-11-30 | 2017-06-08 | Abbvie Inc. | Conjugués anticorps-medicaments anti-hulrrc15 et procédés d'utilisation de ces conjugués |
| AU2017342559B2 (en) * | 2016-10-14 | 2022-03-24 | Xencor, Inc. | Bispecific heterodimeric fusion proteins containing IL-15/IL-15Ralpha Fc-fusion proteins and PD-1 antibody fragments |
| UA125700C2 (uk) | 2017-04-03 | 2022-05-18 | Ф. Хоффманн-Ля Рош Аг | Імунокон'югати антитіла до pd-1 з мутантом il-2 |
| WO2019166946A1 (fr) | 2018-02-28 | 2019-09-06 | Pfizer Inc. | Variants d'il-15 et leurs utilisations |
| WO2019166617A1 (fr) * | 2018-03-01 | 2019-09-06 | Glycotope Gmbh | Constructions de protéines de fusion comprenant un anticorps anti-muc1 et de l'il -15 |
| CN112105645A (zh) * | 2018-04-18 | 2020-12-18 | Xencor股份有限公司 | Il-15/il-15ra异二聚体fc融合蛋白及其用途 |
| US11377477B2 (en) * | 2018-10-12 | 2022-07-05 | Xencor, Inc. | PD-1 targeted IL-15/IL-15RALPHA fc fusion proteins and uses in combination therapies thereof |
| US11738050B2 (en) | 2019-02-01 | 2023-08-29 | Regents Of The University Of Minnesota | Compounds binding to fibroblast activation protein alpha |
| KR20220069018A (ko) * | 2019-09-25 | 2022-05-26 | 레토 래버러토리즈 컴퍼니 리미티드 | 재조합 인터류킨-15 유사체 |
-
2022
- 2022-06-23 CA CA3221886A patent/CA3221886A1/fr active Pending
- 2022-06-23 AU AU2022296794A patent/AU2022296794A1/en active Pending
- 2022-06-23 BR BR112023027312A patent/BR112023027312A2/pt unknown
- 2022-06-23 EP EP22736247.2A patent/EP4359428A2/fr active Pending
- 2022-06-23 WO PCT/EP2022/067236 patent/WO2022268983A2/fr active Application Filing
- 2022-06-23 KR KR1020247002543A patent/KR20240024242A/ko unknown
- 2022-06-23 IL IL309533A patent/IL309533A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA3221886A1 (fr) | 2022-12-29 |
| BR112023027312A2 (pt) | 2024-03-12 |
| EP4359428A2 (fr) | 2024-05-01 |
| WO2022268983A3 (fr) | 2023-04-06 |
| KR20240024242A (ko) | 2024-02-23 |
| IL309533A (en) | 2024-02-01 |
| WO2022268983A2 (fr) | 2022-12-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11377477B2 (en) | PD-1 targeted IL-15/IL-15RALPHA fc fusion proteins and uses in combination therapies thereof | |
| US10669344B2 (en) | Engineered antibodies and other Fc-domain containing molecules with enhanced agonism and effector functions | |
| IL268836B2 (en) | Bispecific molecules that bind CD137 and cancer antigens and their uses | |
| JP2019517539A (ja) | 併用療法 | |
| TW201730212A (zh) | Ｒｏｒ１－結合分子及其使用方法 | |
| CN116333138A (zh) | Pd-1结合分子和其使用方法 | |
| US20230227584A1 (en) | Bispecific antibodies comprising a modified c-terminal crossfab fragment | |
| WO2021202675A1 (fr) | Cytokines il-2 masquées et leurs produits de clivage | |
| US20230072822A1 (en) | Tumor-specific cleavable linkers | |
| AU2020351205A1 (en) | Multimeric antibodies with enhanced selectivity for cells with high target density | |
| KR20220079904A (ko) | 특성이 개선된 pd-1 표적 il-15/il-15r 알파 fc 융합 단백질 | |
| IL296225A (en) | Binding molecules in the fc domain that activate the immune system | |
| TW202000231A (zh) | 變體ｃｄ３-結合結構域及其在用於治療疾病的組合療法中的用途 | |
| JP2021505637A (ja) | 二重特異性ｃｄ１６結合分子、及び疾患の治療におけるその使用 | |
| KR20190099247A (ko) | Adam9-결합 분자, 및 이것의 사용 방법 | |
| EP4359428A2 (fr) | Immunocytokines à base d'interleukine-15 | |
| JP2023547506A (ja) | Ｂ細胞悪性腫瘍を治療するための抗ｃｄ１９剤及びｂ細胞標的化剤の組み合わせ療法 | |
| JP2024524891A (ja) | インターロイキン－１５に基づく免疫サイトカイン | |
| CN117597356A (zh) | 基于白细胞介素-15的免疫细胞因子 | |
| WO2022268991A1 (fr) | Variants d'interleukine 15 | |
| RU2805648C2 (ru) | Биспецифические связывающие молекулы, способные связывать cd137 и опухолевые антигены, и варианты их применения | |
| WO2024094741A1 (fr) | Polythérapie avec un anticorps bispécifique anti-cd19/anti-cd28 | |
| CN115279403A (zh) | Cd137结合分子及其用途 |